Low-Dose Nivolumab Added to Metronomic Chemotherapy Improves OS in Advanced Head and Neck Squamous Cell Carcinoma

According to a phase 3 study, adding low-dose nivolumab to metronomic chemotherapy improves overall survival (OS) in patients with advanced head and neck squamous cell carcinoma.

Metronomic chemotherapy was shown to improve in this patient population in a prior study and retrospective data suggest that low-dose nivolumab could be efficacious in this setting. “Hence, we aimed to assess whether the addition of low-dose nivolumab to triple metronomic chemotherapy improved OS,” wrote Vijay Maruti Patil, MD, Tata Memorial Hospital, Mumbai, India, et al.

The study included 151 patients with recurrent or newly diagnosed advanced head and neck squamous cell treated with palliative intent. Patients were randomized on a 1:1 basis to either triple metronomic chemotherapy (9 mg/m² methotrexate orally once a week, 200 mg celecoxib twice daily, and 150 mg erlotinib once daily; n = 75) or triple metronomic chemotherapy with 20 mg nivolumab intravenously once every 3 weeks (n = 76). The primary end point was OS at 1 year.

The median follow-up duration was 10.9 months. The 1-year OS of the added nivolumab arm was 43.4% (95% confidence interval [CI], 30.8 to 55.3), compared to 16.3% (95% CI, 8 to 27.4) of the triple metronomic chemotherapy alone arm (hazard ratio [HR] 0.545; 95% CI, 0.362 to 0.820; P = .0036). The median OS in the added nivolumab arm was 10.1 months (95% CI, 7.4 to 12.6) compared to 6.7 months (95% CI, 5.8 to 8.1) in the triple metronomic chemotherapy alone arm (P = .0052).

Grade ≥3 adverse events occurred in 46% of patients in the added nivolumab arm and 50% in the triple metronomic chemotherapy alone arm (P = .744). The most common grade ≥3 adverse events in both arms were hyponatremia (27% in the added nivolumab arm vs 30.3% in the triple metronomic chemotherapy group), rash (12.2% vs 9.2%), and anemia (10.8% vs 17.1%).

Dr Patil et al added, “The addition of low-dose nivolumab to metronomic chemotherapy did not lead to an increase in adverse events and also led to an increase in multiple domains of quality of life” and that “use of the [triple metronomic chemotherapy plus low-dose nivolumab] regimen decreases the cost of therapy to 5%-9% of the cost of full-dose immunotherapy regimens.” They concluded that this treatment “is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.”

Source:

Patil VM, Noronha V, Menon N, et al. Low-dose immunotherapy in head and neck cancer: A randomized study. J Clin Oncol. Published online October 20, 2022 doi:10.1200/JCO.22.01015